The present invention relates to a pyrrolidine derivative and a pharmacologically acceptable salt thereof which exhibits excellent pharmaceutical activities.
About 20% of the Japanese at large, i.e., about 20 million or more Japanese are suffering from hypertension which is an important risk factor of various cerebral diseases, cardiac diseases, etc. At the present time, hypotensive and diuretic agents, .beta.-blockers, Ca antagonists, ACE inhibitors, etc. are actually used for clinical purposes in the pharmacotherapy for hypertension.
However, there are a wide variety of origins and pathological conditions on the hypertension, and it is very difficult to significantly control all the types of hypertensions with only one drug. Further, with respect to safety, for example, the .beta.-blocker exhibits side effects such as cardiac depression and bronchoconstriction, while the diuretic agent exhibits side effects such as hyperuricemia, saccharometabolism disorder, and lipid metabolism disorder.
Under these circumstances, better hypotensive drugs different from one another in the mechanism of action have been still desired.
In view of the above, the present inventors have made extensive and intensive studies for years particularly on a dopamine 1 agonist with a view to developing a hypotensive drug, particularly one having a renal blood flow increasing activity and, as a result, have found that a pyrrolidine derivative which will be described hereinbelow exhibits an excellent activity.
Pyrrolidine derivatives having a hypotensive activity are scarcely known in the art.
Although U.S. Pat. No. 2,852,526 discloses a pyrrolidine derivative, this compound is different from the compound of the invention in chemical structure and remarkably different also in the pharmaceutical effect, as is apparent from the fact that the U.S. Patent describes only that the compound exhibits bronchodilator, antihistaminic, and anticholinergic activities.
Although Fenoldopam (SKF-82526) has been proposed as a compound having a renal blood flow increasing activity, this compound is a benzazepine compound and different from the compound of the present invention in the structure.